Diisopropylethylamine → HCID 178446422, compound

HRID 2169336Notes

Reaction equation

HRID 2169336 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:28](O)=[O:29])=[N:11][C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:13][C:14]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si:31]([O:38][CH2:39][CH2:40][NH:41][CH2:42][C:43]([CH3:46])([CH3:45])[CH3:44])([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O.O>[Si:31]([O:38][CH2:39][CH2:40][N:41]([CH2:42][C:43]([CH3:46])([CH3:45])[CH3:44])[C:28]([C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:14]([OH:15])[N:13]=[C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)[N:11]=1)=[O:29])([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:32])[CH3:33]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86725974[2-(tert-Butyl-dimethylsilanyloxy)-ethyl]-(2,2-dimethyl-propyl)-amineHCID 178524866HCID 178524866, compound

Product 1

HCID 178446422HCID 178446422, compoundYield 86.27%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution mixture of 5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid (283) (230 mg, 0.57 mmol) and [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-(2,2-dimethyl-propyl)-amine (8h) (167 mg, 0.68 mmol) in dimethylformamide (2.2 mL) were added N,N-diisopropylethylamine (0.3 mL, 1.70 mmol) and HATU (324 mg, 0.85 mmol). The reaction was stirred at room temperature for 20 h. Water (75 mL) was added and the mixture was extracted with ethyl acetate (3×20 mL). The combined organic part was washed with water (3×50 mL) and brine (2×30 mL) and dried and concentrated. The crude product was purified by Combi-Flash column (eluted at 20-30% ethyl acetate in hexane) to get 5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-(2,2-dimethyl-propyl)-amide (300) (310 mg, 86.27%) as an off-white sticky solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×20 mL)
  2. washThe combined organic part was washed with water (3×50 mL) and brine (2×30 mL)
  3. customdried
  4. concentrationconcentrated
  5. customThe crude product was purified by Combi-Flash column (eluted at 20-30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-83f6b7fcd84f4a578d61347192dae877
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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